Evaluating the Safety of Alemtuzumab as a Treatment for Multiple Sclerosis

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The use of alemtuzumab as an immunotherapy for multiple sclerosis (MS) has been linked to serious side effects. A new study explains how alemtuzumab might trigger new autoimmune disease as the immune system reconstitutes itself after administration.

Multiple sclerosis (MS) is an autoimmune disease which causes damage to the central nervous system by eating away at myelin, the fatty layer that electrically insulates nerve cells and allows for the transmission of nerve impulses. When a substantial amount of myelin is lost, nerve signals between the brain and the body are interrupted and muscle function is disrupted or gradually lost. Since MS affects the central nervous system, virtually any neurologic function can be negatively affected. As such, common symptoms of MS include muscle weakness, loss of sensation, impaired coordination and vision, and incontinence.

Unfortunately, there is no cure for MS and treatments are limited. Therapeutic and technological advances help people with MS to better manage their symptoms. In addition, clinical research has led to the development of some medications which have been shown to slow the progression of the disease. One such medication is alemtuzumab.

Alemtuzumabis a humanized monoclonal antibody directed at CD52, a protein on the surface of immune cells. It was first approved (at much higher doses) as a treatment for B-cell chronic lymphocytic leukemia. Typically, alemtuzumab is initially administered daily for five consecutive days. Follow up treatment involves daily administration for 3-5 days at intervals ranging from monthly to once a year. Alemtuzumab causes rapid and prolonged lymphocyte depletion. In turn, the body produces new lymphocytes and auto reactive T cells. In 2014, alemtuzumab was approved for the treatment of relapsing MS since clinical trials research had shown it to be effective at inhibiting the progression of the disease.

Regrettably, this research has also indicated that the use of alemtuzumab for MS can lead to serious adverse events (SAEs).For example, it has been associated with long-term severe (greater than 80%) depletion of memory B and T cells which help the immune system to remember pathogens for faster antibody production in future infections. Additional SAEs associated with alemtuzumab include an increased risk for autoimmune thyroid disorders and immune thrombocytopenia, a rare bleeding condition.

In a study published in JAMA Neurology, an English research team led by Dr. David Baker analyzed how T and B cell populations were affected by alemtuzumab and how they returned after the course of therapy.They found that controlling B-cell proliferation until T-cell regulation recovers may limit the SAEs associated with alemtuzumab. Based on this observation, they hypothesize that autoimmune diseases, in general, may arise from B-cell development without adequate control from regulatory T-cells.

Clearly, the use of alemtuzumab for MS requires careful monitoring so that potential SAEs can be treated early and effectively. By building upon this study explaining the mechanisms by which alemtuzumab might trigger new autoimmune disease, scientists may be able to develop a diagnostic test to predict the risk of an SAE. Further investigation of their hypothesis regarding the generalized mechanisms of autoimmune diseases will hopefully lead to the development of better treatments and maybe even a cure.

Written by Debra A. Kellen, PhD

I was given an editorial summary by Lawrence Steinman. The original article’s citation is:

Baker, D., Herrod, S. S., Alvarez-Gonzalez, C., Giovannoni, G., &Schmierer, K. (2017). Interpreting lymphocyte reconstitution data from the pivotal phase 3 trials of alemtuzumab. JAMA neurology.

JAMA Neurol. doi:10.1001/jamaneurol.2017.0676 [published online June 12, 2017]

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